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6jp5

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Revision as of 02:13, 11 April 2020

Rabbit Cav1.1-Nifedipine Complex

6jp5, resolution 2.90Å

Structural highlights

6jp5 is a 5 chain structure with sequence from European rabbit and Oryctolagus cuniculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	CACNB1, CACNLB1 (European rabbit)
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[CAC1S_RABIT] Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1S gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin-GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing the alpha-1S subunit play an important role in excitation-contraction coupling in skeletal muscle. [CA2D1_RABIT] The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Plays an important role in excitation-contraction coupling. [CCG1_RABIT] This protein is a subunit of the dihydropyridine (DHP) sensitive calcium channel. Plays a role in excitation-contraction coupling. The skeletal muscle DHP-sensitive Ca(2+) channel may function only as a multiple subunit complex.

Publication Abstract from PubMed

The L-type voltage-gated Ca(2+) (Cav) channels are modulated by various compounds exemplified by 1,4-dihydropyridines (DHP), benzothiazepines (BTZ), and phenylalkylamines (PAA), many of which have been used for characterizing channel properties and for treatment of hypertension and other disorders. Here, we report the cryoelectron microscopy (cryo-EM) structures of Cav1.1 in complex with archetypal antagonistic drugs, nifedipine, diltiazem, and verapamil, at resolutions of 2.9 A, 3.0 A, and 2.7 A, respectively, and with a DHP agonist Bay K 8644 at 2.8 A. Diltiazem and verapamil traverse the central cavity of the pore domain, directly blocking ion permeation. Although nifedipine and Bay K 8644 occupy the same fenestration site at the interface of repeats III and IV, the coordination details support previous functional observations that Bay K 8644 is less favored in the inactivated state. These structures elucidate the modes of action of different Cav ligands and establish a framework for structure-guided drug discovery.

Molecular Basis for Ligand Modulation of a Mammalian Voltage-Gated Ca(2+) Channel.,Zhao Y, Huang G, Wu J, Wu Q, Gao S, Yan Z, Lei J, Yan N Cell. 2019 May 30;177(6):1495-1506.e12. doi: 10.1016/j.cell.2019.04.043. PMID:31150622^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Zhao Y, Huang G, Wu J, Wu Q, Gao S, Yan Z, Lei J, Yan N. Molecular Basis for Ligand Modulation of a Mammalian Voltage-Gated Ca(2+) Channel. Cell. 2019 May 30;177(6):1495-1506.e12. doi: 10.1016/j.cell.2019.04.043. PMID:31150622 doi:http://dx.doi.org/10.1016/j.cell.2019.04.043

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6jp5"

@@ Line 3: / Line 3: @@
 <SX load='6jp5' size='340' side='right' viewer='molstar' caption='[[6jp5]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6jp5]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/European_rabbit European rabbit] and [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6JP5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6JP5 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6jp5]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/European_rabbit European rabbit] and [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6JP5 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6JP5 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3PE:1,2-DIACYL-SN-GLYCERO-3-PHOSPHOETHANOLAMINE'>3PE</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=C5U:dimethyl+2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate'>C5U</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=ETA:ETHANOLAMINE'>ETA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PC1:1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE'>PC1</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3PE:1,2-DIACYL-SN-GLYCERO-3-PHOSPHOETHANOLAMINE'>3PE</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=C5U:dimethyl+2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate'>C5U</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=ETA:ETHANOLAMINE'>ETA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PC1:1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE'>PC1</scene></td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CACNB1, CACNLB1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9986 European rabbit])</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6jp5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jp5 OCA], [http://pdbe.org/6jp5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6jp5 RCSB], [http://www.ebi.ac.uk/pdbsum/6jp5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6jp5 ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6jp5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jp5 OCA], [http://pdbe.org/6jp5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6jp5 RCSB], [http://www.ebi.ac.uk/pdbsum/6jp5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6jp5 ProSAT]</span></td></tr>
 </table>
 == Function ==

6jp5

From Proteopedia

Revision as of 02:13, 11 April 2020

Rabbit Cav1.1-Nifedipine Complex

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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